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1.
Arthritis Care Res (Hoboken) ; 66(9): 1380-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24515659

RESUMO

OBJECTIVE: Patients with systemic sclerosis (SSc; scleroderma) are at high risk for the development of ischemic digital ulcers (DUs), which occur in 35-60% of SSc patients. The aim of this study was to assess the correlation between intrarenal arterial stiffness and DUs in SSc patients and to evaluate the prognostic value of Doppler indices to predict new DU occurrence. METHODS: Seventy unselected, consecutive patients with SSc (58 women and 12 men, mean ± SD age 49.5 ± 13.8 years) were enrolled. In all patients, Doppler ultrasound examination was performed. The following Doppler indices of intrarenal stiffness were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D). RESULTS: In total, 30 (42%) of 70 patients experienced new DUs. RI, S/D, and PI were significantly higher in SSc patients with new DUs than in SSc patients without new DUs. The receiver operating characteristic (ROC) curves demonstrated a good accuracy of new DU prediction for RI (0.94, P < 0.0001), S/D (0.92, P < 0.0001), and PI (0.88, P < 0.0001). Conversely, the ROC curve showed no performance for PSV (0.58, P > 0.05) and EDV (0.28, P > 0.05). Using a cutoff value of 0.70 for RI and 3.25 for S/D, the positive predictive value was 90.6% and 92.9%, respectively. CONCLUSION: We can conclude that Doppler indices of intrarenal stiffness are reliable markers of new DU occurrence. Doppler indices could be used in association with the capillaroscopic and clinical findings or serologic tests for the identification of patients at high risk of developing DUs.


Assuntos
Escleroderma Sistêmico/complicações , Úlcera Cutânea/etiologia , Rigidez Vascular/fisiologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia , Úlcera Cutânea/patologia , Úlcera Cutânea/fisiopatologia
2.
Rheumatology (Oxford) ; 52(12): 2238-42, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24030011

RESUMO

OBJECTIVES: The objectives of this study were to investigate clitoral blood flow in SSc women compared with healthy controls and to correlate it with microvascular damage and disease clinical variables. We also evaluated the correlation between clitoral blood flow and sexual dysfunction. METHODS: Twenty-two SSc women and 20 healthy controls matched for sex and age were enrolled in this study. Baseline Doppler indices of the clitoral artery were measured. Peak systolic velocity, end diastolic velocity, resistive index (RI), pulsatile index (PI) and systolic/diastolic (S/D) ratio were measured. The female sexual function index (FSFI) was used to assess sexual function. RESULTS: The RI and S/D ratio were higher (P < 0.0001) in SSc women compared with healthy controls. The PI, RI and S/D ratio increased with progression of capillaroscopic damage. The RI and S/D ratio were higher (P < 0.01) in women with digital ulcers than in women without digital ulcers. No correlation exists between Doppler indices of the clitoral artery and age or clinical variables of disease. The FSFI was reduced in 7 (32%) of 22 SSc women. A negative correlation was observed between both the FSFI and RI (R = -0.74, P < 0.0001) and the S/D ratio (R = -0.68, P < 0.0001). A negative correlation exists between the RI and all domains of the FSFI score except for desire. CONCLUSION: Clitoral blood flow was reduced in SSc women compared with healthy controls. Clitoral blood flow was reduced in SSc women with digital ulcers and it correlated with capillaroscopic damage progression. A negative correlation exists between the RI and S/D ratio and all domains of the FSFI score except for desire.


Assuntos
Clitóris/irrigação sanguínea , Escleroderma Sistêmico/fisiopatologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Ultrassonografia Doppler Dupla
3.
PLoS One ; 8(9): e74332, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24058548

RESUMO

Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERß, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular, the percentage of activated Treg (CD4(+)CD45RA(-) FoxP3(bright)CD25(bright)) was significantly higher in anti-ERα antibody positive patients than in anti-ERα antibody negative patients. Taken together our data clearly indicate that anti-ERα antibodies, probably via the involvement of membrane-associated ER, can represent: i) promising markers for SSc progression but, also, ii) functional modulators of the SSc patients' immune system.


Assuntos
Autoanticorpos/sangue , Progressão da Doença , Receptor alfa de Estrogênio/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Adulto , Idoso , Autoanticorpos/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Demografia , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Adulto Jovem
4.
J Sex Med ; 10(5): 1380-8, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23444914

RESUMO

INTRODUCTION: Erectile dysfunction (ED) prevalence in men with systemic sclerosis (SSc) is high and can be considered a manifestation of endothelium damage. AIM: This study aims to correlate ED with endothelial dysfunction and digital vascular damage in SSc patients. MAIN OUTCOME MEASURES: The main outcome measures were erectile function, Doppler indices of cavernous arteries, flow-mediated dilation (FMD), capillaroscopic damage, skin perfusion, and digital pulsatility. METHODS: In 23 SSc patients, erectile function was investigated using the International Index of Erectile Function-5 (IIEF-5). Doppler indices of cavernous arteries, peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were measured at the penoscrotal junction before and after pharmacostimulation with 20 mg prostaglandin E1. FMD and nailfold videocapillaroscopy (NVC) were used to evaluate endothelial dysfunction and capillaroscopic damage. Skin perfusion and digital sphygmic waves were measured by laser Doppler perfusion imaging (LDPI) and digital photoplethysmography (PPG), respectively. RESULTS: IIEF-5 score was reduced in 83% of patients. PSV was reduced in 96%, while EDV was increased in 48% of patients. A positive correlation was observed between IIEF-5 score and FMD (r = 0.71, P < 0.0001) and between the former and PSV (r = 0.76, P < 0.0001). A negative correlation was observed between EDV and FMD (r = -0.509, P < 0.01). FMD and Doppler indices were reduced with capillaroscopic damage progression. A positive correlation exists between LDPI perfusion and IIEF-5 score (r = 0.743, P < 0.0001) and between the former and PSV (r = 0.714, P < 0.0001), while a negative correlation is observed between LDPI perfusion and EDV (r = -0.677, P < 0.0001). A positive correlation exists between PPG pulsatility and IIEF-5 score (r = 0.752, P < 0.0001) and between the former and PSV (r = 0.747, P < 0.0001), while negative correlation is observed between PPG pulsatility and EDV (r = -0.689, P < 0.0001). CONCLUSION: In SSc patients, ED correlates with endothelial dysfunction and digital microvascular damage.


Assuntos
Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Disfunção Erétil/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Adulto , Idoso , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fotopletismografia , Ultrassonografia Doppler
6.
Semin Arthritis Rheum ; 41(6): 815-21, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22192932

RESUMO

OBJECTIVES: To evaluate intrarenal arterial stiffness by Doppler ultrasound and examine the correlation between renal Doppler indices, glomerular filtration rate, and digital microvascular damage in systemic sclerosis patients. METHODS: Thirty systemic sclerosis patients and 30 healthy controls were enrolled in this study. Doppler indices of intrarenal arterial stiffness, peak systolic flow velocity, end diastolic flow velocity, resistive index, pulsative index, and systolic/diastolic (S/D) ratio were measured on the interlobar artery of both kidneys. Glomerular filtration rate was measured using Tc(99m) diethylenetriamine pentaacetic acid (DTPA). Equation 7 from the Modification of Diet in Renal Disease was used to estimate glomerular filtration rate. Nailfold videocapillaroscopy findings were classified as early, active, and late patterns. RESULTS: The intrarenal arterial stiffness, evaluated by Doppler indices, was higher in systemic sclerosis patients than healthy controls. In systemic sclerosis patients pulsative index (r = -0.69), resistive index (r = -0.75), and S/D ratio (r = -0.74) showed a negative correlation with measured glomerular filtration rate (P < 0001). High correlation (P = 0008) was observed between measured and estimated glomerular filtration rate (r = 0.55). Pulsative index, resistive index, and S/D ratio significantly increased with progression of capillaroscopic damage. Conversely, measured glomerular filtration rate significantly decreased with capillaroscopic damage progression. CONCLUSIONS: Doppler indices of intrarenal arterial stiffness are noninvasive diagnostic tests to evaluate renal damage in SSc patients. Intrarenal arterial stiffness and glomerular filtration rate correlate with capillaroscopic microvascular damage.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Hemodinâmica/fisiologia , Rim/irrigação sanguínea , Circulação Renal/fisiologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico por imagem , Ultrassonografia , Rigidez Vascular/fisiologia
7.
Microvasc Res ; 82(3): 410-5, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21816163

RESUMO

OBJECTIVE: To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by color Doppler ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls. METHODS: CDUS, NVC, laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls. RESULTS: CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p<0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvascular damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings. CONCLUSION: PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.


Assuntos
Dedos/irrigação sanguínea , Microvasos/patologia , Doença Arterial Periférica/patologia , Escleroderma Sistêmico/patologia , Adulto , Artérias/patologia , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Itália , Fluxometria por Laser-Doppler , Masculino , Microcirculação , Angioscopia Microscópica , Microvasos/diagnóstico por imagem , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Fotopletismografia , Valor Preditivo dos Testes , Fluxo Pulsátil , Fluxo Sanguíneo Regional , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Escleroderma Sistêmico/fisiopatologia , Ultrassonografia Doppler em Cores
8.
Eur J Intern Med ; 22(3): 318-21, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21570655

RESUMO

BACKGROUND: The prevalence of erectile dysfunction (ED) in men with systemic sclerosis (SSc) can be considered a manifestation of endothelium damage. Aim of the study is to investigate ED in SSc patients by color Doppler ultrasound examination and to correlate it with disease severity and digital vascular damage. METHODS: In 20 males SSc patients blood flow velocity in the cavernous artery was determined with Duplex ultrasonography. Naifold videocapillaroscopy, Sexual Health Inventory for Men (SHIM) and Medsger Disease Severity Scale (DSS) were performed. Arteriogenic ED was defined by the presence of a reduced peak systolic velocity (PSVs), while diastolic velocity (EDV) and the resistive index (RI) were estimated to evaluate venocclusive dysfunction. SSc patients are classified by capillaroscopic pattern and vascular domain of DSS into two groups: low vascular damage (early or active capillaroscopic pattern and score of vascular domain of DSS≤2) and high vascular damage (late capillaroscopic pattern and score of vascular domain of DSS≥3). RESULTS: In all SSc patients a reduction of SHIM is present (mean 13.5±6.3). Patients with less vascular damage have a significantly (p<0.001) higher score of SHIM than patients with greater vascular damage (19.2±2.4 vs 7.9±2.7). No significant difference (p>0.5) between the two groups of vascular damage was found in PSVs. Venocclusive dysfunction was present only (p<0.001) in the group with high vascular damage. CONCLUSION: We can assert that there is a relationship between SSc vascular digital damage and ED.


Assuntos
Impotência Vasculogênica/diagnóstico por imagem , Pênis/irrigação sanguínea , Doença de Raynaud/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Índice de Gravidade de Doença , Adulto , Artérias/diagnóstico por imagem , Disfunção Erétil/diagnóstico por imagem , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Pênis/diagnóstico por imagem , Ultrassonografia Doppler em Cores
9.
Rheumatology (Oxford) ; 50(9): 1654-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21622523

RESUMO

OBJECTIVES: To assess by Laser Doppler perfusion imaging (LDPI) skin blood perfusion of hands in patients with SSc and primary RP (PRP) at baseline and after cold stimulation (CS). In SSc patients, the associations between skin perfusion and nailfold video capillaroscopy (NVC) patterns were also evaluated. METHODS: Forty patients with SSc, 38 patients with PRP and 32 healthy controls were recruited. Skin blood flow of the hands was detected by Lisca Laser Doppler Perfusion Imager at baseline and after CS. Further laser Doppler scanning was performed for each hand at 0 (T(1)), 3 (T(2)), 7 (T(3)) and 15 min (T(4)). RESULTS: Baseline mean perfusion is significantly (P < 0.000 l) lower in SSc patients than in healthy controls. In SSc patients, mean perfusion is reduced after CS (P < 0.0001) and skin flow recovery (significant difference between T(0) and T(4), P < 0.0001) is incomplete. In SSc patients with low vascular damage (early and active capillaroscopic groups), the abnormal microvascular response to CS involves only the digits, while the perfusion of hands dorsum is normal. With the progression of vascular damage (late capillaroscopic groups), the abnormal microvascular response to CS also appears in the hand dorsum skin. In PRP patients, baseline hand perfusion is very low and the skin flow recovery after CS is absent (P < 0.05). CONCLUSION: In early SSc, the thermoregulation of finger skin is impaired, but only in advanced stages of microangiopathy does the skin of the hand dorsum show a vasomotor control failure.


Assuntos
Dedos/irrigação sanguínea , Unhas/irrigação sanguínea , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Pele/irrigação sanguínea , Adulto , Idoso , Estudos de Casos e Controles , Temperatura Baixa , Feminino , Mãos/irrigação sanguínea , Humanos , Fluxometria por Laser-Doppler/métodos , Masculino , Microcirculação , Angioscopia Microscópica/métodos , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Doença de Raynaud/complicações , Escleroderma Sistêmico/complicações , Adulto Jovem
10.
Intern Med ; 50(7): 767-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21467714

RESUMO

Digital ulcers (DUs) and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis. Raynaud's phenomenon (RP) is an almost universal manifestation of systemic sclerosis, with 95% of all patients being affected, and resulting in DUs in approximately 30% of the patients each year. Although RP may be present in approximately 25-50% of the patients, DUs are relatively rare in systemic lupus erythematosus (SLE) and never present as an initial manifestation of disease. In this case report DUs appear as the initial manifestation of SLE in a young woman with a capillaroscopic scleroderma pattern and elevated systolic pulmonary arterial pressure.


Assuntos
Dedos , Lúpus Eritematoso Sistêmico/complicações , Dermatopatias/etiologia , Úlcera/etiologia , Adulto , Capilares/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Doença de Raynaud/diagnóstico , Doença de Raynaud/etiologia , Pele/irrigação sanguínea , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Resultado do Tratamento , Úlcera/diagnóstico , Úlcera/tratamento farmacológico
11.
J Rheumatol ; 37(12): 2531-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20810512

RESUMO

OBJECTIVE: Our aim was to investigate effects of bosentan on hand perfusion in patients with systemic sclerosis (SSc) with pulmonary arterial hypertension (PAH), using laser Doppler perfusion imaging (LDPI). METHODS: We enrolled 30 SSc patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc patients and healthy controls at baseline, skin blood flow of the dorsum of the hands was determined with a Lisca laser Doppler perfusion imager. The dorsal surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included 3 fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint. ROI 2 included the area between the proximal interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal surface of the hand without the fingers. LDPI was repeated in SSc patients and controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline and at 4, 8, and 16 weeks. RESULTS: SSc patients with PAH enrolled in the study received treatment with bosentan as standard care for PAH. In these patients with PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to be most effective in patients with the early and active capillaroscopic pattern than in patients with the late pattern. Bosentan improved skin blood flow principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the perfusion proximal-distal gradient in 57% of SSc patients with the early capillaroscopic pattern. No significant differences from baseline were observed in the RCS in SSc patients with PAH. CONCLUSION: Bosentan improved skin perfusion in SSc patients with PAH, although it did not ameliorate symptoms of Raynaud's phenomenon. Skin blood perfusion increased in SSc patients with PAH, particularly in the skin region distal to the proximal interphalangeal joint, and in patients with the early/active capillaroscopic pattern. Double-blind randomized clinical trials are needed to evaluate the effects of bosentan on skin perfusion of SSc patients without PAH and with active digital ulcers.


Assuntos
Anti-Hipertensivos , Hipertensão Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Sulfonamidas , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Bosentana , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/tratamento farmacológico , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Fluxo Sanguíneo Regional , Escleroderma Sistêmico/fisiopatologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
12.
Am J Med Sci ; 340(6): 457-61, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20811271

RESUMO

INTRODUCTION: The aim of this study is to investigate pulsatility of digital arteries of hands by means of photoplethysmography (PPG) in patients with primary Raynaud phenomenon (PRP) and systemic sclerosis (SSc) and to compare the results with those obtained in healthy controls. METHODS: One hundred five patients with SSc, 96 patients with PRP and 85 healthy controls were recruited in this study. Nailfold videocapillaroscopy and PPG were performed in healthy controls and patients. In patients with SSc, the capillaroscopic pattern was classified as early, active and late group pattern. A baseline PPG was recorded simultaneously in all 10 fingers of the hands. The photoplethysmographic curves were evaluated for morphology and amplitude of sphygmic wave. RESULTS: In healthy controls group, PPG shows the presence of photoplethysmographic homogeneous pattern and high mean value of sphygmic wave amplitude. In PRP group, PPG demonstrates homogeneous photoplethysmographic pattern and low mean value of sphygmic wave amplitude. Finally, in the SSc group, photoplethysmographic pattern is dyshomogeneous, and the mean value of sphygmic wave amplitude is intermediate between the other 2 groups. The PPG findings are different in the 3 capillaroscopic groups of patients with SSc and 2 subsets of disease. CONCLUSION: PPG represents a technique noninvasive to evaluate simultaneously in all 10 fingers of hands digital arteries pulsatility. PPG improves the evaluation of vascular damage in patients with primary and sclerodermic RP.


Assuntos
Fotopletismografia/métodos , Doença de Raynaud/diagnóstico , Escleroderma Sistêmico/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/fisiopatologia
13.
Clin Immunol ; 137(1): 122-33, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20580318

RESUMO

We investigated in systemic sclerosis (SSc) patients the T cell homeostasis and its relationship with the clinical course of the disease. Distribution of peripheral T cell subsets, thymic output, lymphocyte proliferation and apoptosis were analyzed by flow cytometry or ELISA. Age inappropriate levels of naive CD4(+) T cells and thymic output were observed. Proliferation of CD4(+) T cells, lymphocyte apoptosis and CD4(+) regulatory T (Treg) cell frequency were significantly higher than those observed in controls and significantly correlated with clinical phenotypes and clinical progression parameters i.e., diffusing capacity of the lung for carbon monoxide (DLCO) and disease activity. These data indicate that the evaluation of the T cell homeostasis can represent a valuable prognostic tool for SSc patients and it is useful to distinguish between limited and diffuse phenotypes. A therapeutic intervention targeted at reversing T cell homeostasis abnormalities would therefore potentially be helpful in counteracting disease progression.


Assuntos
Homeostase/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/fisiopatologia , Linfócitos T/imunologia , Linfócitos T/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Apoptose/imunologia , Contagem de Linfócito CD4 , Monóxido de Carbono/metabolismo , Proliferação de Células , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Troca Gasosa Pulmonar/fisiologia , Esclerodermia Difusa/sangue , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/sangue , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/imunologia , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Adulto Jovem
15.
Acta Pharmacol Sin ; 30(9): 1283-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19730428

RESUMO

AIM: To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. METHODS: In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g x kg(-1) x h(-1). Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. RESULTS: NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. CONCLUSION: In patients with low disease severity NAC ameliorates vascular renal function.


Assuntos
Acetilcisteína/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Obstrução da Artéria Renal/tratamento farmacológico , Escleroderma Sistêmico/complicações , Feminino , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Artéria Renal/efeitos dos fármacos , Artéria Renal/fisiologia , Obstrução da Artéria Renal/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Resistência Vascular/efeitos dos fármacos
16.
J Rheumatol ; 36(10): 2257-63, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19684154

RESUMO

OBJECTIVE: To investigate capillary morphology and skin blood flow of dorsal hands by nailfold videocapillaroscopy (NVC) and laser Doppler perfusion imaging (LDPI), respectively, in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc) and to compare the results with those obtained in healthy controls. METHODS: The study group consisted of 142 patients with SSc, 88 patients with PRP, and 147 healthy controls. NVC was performed in all the groups examined. In patients with SSc the capillaroscopic pattern was classified as early, active, or late group pattern. A baseline skin blood flow determination of the dorsum of the subject's hands was acquired through a low-energy 670 nm Lisca Laser Doppler Perfusion Imager. RESULTS: In the healthy controls the perfusion distribution pattern was homogeneous, with a proximal-distal perfusion gradient. In patients with PRP, the perfusion distribution pattern was homogeneous, but the proximal-distal perfusion gradient was absent. Finally, in patients with SSc the perfusion distribution pattern was dyshomogeneous and a proximal-distal gradient was absent. The minimum perfusion, mean perfusion, maximum perfusion, and standard deviation, calculated as variation by means of each measurement site, were significantly different in all the groups examinated. CONCLUSION: NVC represents the best method to analyze microvascular damage in rheumatic diseases. LDPI improves the evaluation of vascular damage in patients with SSc. The LDPI and the capillaroscopic images fully matched the definition of the various stages of vascular digital damage in SSc.


Assuntos
Fluxometria por Laser-Doppler/métodos , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Doença de Raynaud/diagnóstico , Doença de Raynaud/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional/fisiologia , Escleroderma Sistêmico/fisiopatologia , Pele/irrigação sanguínea
17.
Clin Rheumatol ; 28(12): 1379-84, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19690939

RESUMO

N-Acetylcysteine is useful in the short-term treatment of severe Raynaud's phenomenon and digital ulcers (DU) in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 3 years) in a prospective study of a cohort of 50 consecutive patients with SSc who received N-acetylcysteine (NAC) infusional therapy every 2 weeks. We observed a reduction of DU/patient/year (4.5 +/- 3.1 vs 0.81 +/- 0.79) and DU ulcer visual analog scale (VAS; 6.88 +/- 2.62 vs 3.20 +/- 1.80), a decrease of the Raynaud's phenomenon (RP) number attacks (7.18 +/- 3.87 vs 3 +/- 1.92), and RP VAS (6.24 +/- 1.92 vs 3.62 +/- 1.48). In this study, we did not observe serious adverse events in patients. Minor side effects were flushing (two patients) and headache (one patient). NAC infusion was generally well tolerated, and nobody had to discontinue the treatment. In conclusion, long-term therapy with NAC, in patients with SSc, has a durable effectiveness on ischemic ulcers and Raynaud's phenomenon.


Assuntos
Acetilcisteína/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Isquemia/tratamento farmacológico , Doença de Raynaud/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Úlcera Cutânea/tratamento farmacológico , Acetilcisteína/administração & dosagem , Feminino , Dedos , Sequestradores de Radicais Livres/administração & dosagem , Humanos , Infusões Intravenosas , Isquemia/complicações , Isquemia/patologia , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/complicações , Doença de Raynaud/patologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/patologia , Pele/irrigação sanguínea , Úlcera Cutânea/complicações , Úlcera Cutânea/patologia , Resultado do Tratamento
18.
J Rheumatol ; 36(5): 965-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19332639

RESUMO

OBJECTIVE: To evaluate the presence of celiac disease in patients with systemic sclerosis (SSc). The association of autoimmune diseases with celiac disease has been reported, but few publications deal with the combination of SSc and celiac disease. METHODS: We investigated the presence of anti-tissue transglutaminase (anti-tTG) antibodies and serum antiendomysial antibodies (anti-EMA) in 50 patients with SSc. All subjects were on a gluten-containing diet. Duodenal mucosa histology and biopsy culture were performed in anti-tTG-positive patients; anti-EMA and IgA, IgG1 anti-tTG were detected in culture supernatants. RESULTS: The incidence of celiac disease in patients with SSc was found to be 8%. Serum anti-tTG antibody-positive results were detectable in 5 out of 50 patients with SSc, but only in 4 of them was the diagnosis confirmed by histological results (Marsh classification). CONCLUSION: Our data show an increased prevalence of celiac disease in patients with SSc.


Assuntos
Doença Celíaca/epidemiologia , Escleroderma Sistêmico/epidemiologia , Adulto , Idoso , Anticorpos Anti-Idiotípicos/análise , Autoanticorpos/sangue , Doença Celíaca/imunologia , Doença Celíaca/patologia , Comorbidade , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mucosa/imunologia , Músculo Liso/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Transglutaminases/imunologia , Adulto Jovem
19.
Rheumatol Int ; 29(8): 913-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19112565

RESUMO

The incidence of left ventricular (LV) diastolic dysfunction is increased in systemic sclerosis (SSc), while systolic dysfunction is present in a small percentage of patients. The aim of this study was to asses the LV "regional" diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for 67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a at DTI was observed in 41. A significant prevalence of DTI diastolic abnormalities in the segments reflecting longitudinal versus those reflecting radial LV motion was found. The segments of the basal regions of LV myocardium were significantly more involved than those of the middle portion. Linear correlation was observed between the extent of the diastolic abnormalities and the duration of disease. Longitudinal myocardial systolic velocities were significantly reduced in patients with abnormal e/a DTI.


Assuntos
Diástole/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Escleroderma Sistêmico/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Ecocardiografia Doppler/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Int Surg ; 90(2): 88-92, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16119712

RESUMO

The authors propose a microsurgical technique to treat upper limb chronic digital ischemia that is resistant to medical therapy. The adventitiectomy technique on digital arteries is used here to remove the fibrous tissue and the vasoconstrictor sympathetic nervous fibers contained in it. This operation is a valid alternative to traditional proximal sympathectomy.


Assuntos
Dedos/patologia , Doença de Raynaud/cirurgia , Simpatectomia/métodos , Adulto , Idoso , Feminino , Dedos/irrigação sanguínea , Humanos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Necrose
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